Our laboratory is focused on the discovery and analysis of structural variation (SVs) from genomic sequence data. As part of the 1000 Genomes Project and other endeavors, we have helped produce initial fine-scale maps using a variety of SV discovery approaches including: (i) paired-end mapping (or read pair analysis) based on abnormally mapped pairs of clone ends; (ii) read-depth analysis, which detects deletions and duplications through analysis of the read depth-of-coverage; (iii) split read analysis, which detects SVs by evaluating gapped sequence alignments; and (iv) sequence assembly, which enables the discovery of novel (non-reference) sequence insertions. We have examined these variants and have been able to assign particular formation mechanisms from the observed breakpoint signatures. We have also identified a number of events which potentially are directly related to particular phenotypes. Our current goals are to improve upon existing methodology in order to detect such events at a sensitivity and specificity level appropriate for use in clinical diagnostics. We are expanding this to the development of new methods to resolve and analyze complex genomic rearrangements, defined as chromosome rearrangements made up from multiple breakpoints. Such regions confound typical analytical approaches and require the development of novel strategies to identify the underlying chromosomal structure. We are also interested in the large-scale integration of genomic, expression, methylation and proteomic data sets.
Iskow RC, McCabe MT, Mills RE, Torene S, Pittard WS, Neuwald AF, Van Meir EG, Vertino PM, Devine SE. Natural mutagenesis of human genomes by endogenous retrotransposons. Cell. 2010 Jun 25;141(7):1253-61. PMC2943760
Park H, Kim JI, Ju YS, Gokcumen O, Mills RE, Kim S, Lee S, Suh D, Hong D, Kang HP, Yoo YJ, Shin JY, Kim HJ, Yavartanoo M, Chang YW, Ha JS, Chong W, Hwang GR, Darvishi K, Kim H, Yang SJ, Yang KS, Kim H, Hurles ME, Scherer SW, Carter NP, Tyler-Smith C, Lee C, Seo JS. Discovery of common Asian copy number variants using integrated high-resolution array CGH and massively parallel DNA sequencing. Nat Genet. 2010 May;42(5):400-5.
1000 Genomes Project Consortium. A map of human genome variation from population-scale sequencing. Nature. 2010 Oct 28;467(7319):1061-73. PMC3042601
Mills RE, Walter K, Stewart C, Handsaker RE, Chen K, Alkan C, Abyzov A, Yoon SC, Ye K, Cheetham RK, Chinwalla A, Conrad DF, Fu Y, Grubert F, Hajirasouliha I, Hormozdiari F, Iakoucheva LM, Iqbal Z, Kang S, Kidd JM, Konkel MK, Korn J, Khurana E, Kural D, Lam HY, Leng J, Li R, Li Y, Lin CY, Luo R, Mu XJ, Nemesh J, Peckham HE, Rausch T, Scally A, Shi X, Stromberg MP, StÃ_tz AM, Urban AE, Walker JA, Wu J, Zhang Y, Zhang ZD, Batzer MA, Ding L, Marth GT, McVean G, Sebat J, Snyder M, Wang J, Ye K, Eichler EE, Gerstein MB, Hurles ME, Lee C, McCarroll SA, Korbel JO; 1000 Genomes Project. Mapping copy number variation by population-scale genome sequencing. Nature. 2011 Feb 3;470(7332):59-65. PMC3077050
Mills RE, Pittard WS, Mullaney JM, Farooq U, Creasy TH, Mahurkar AA, Kemeza DM, Strassler DS, Ponting CP, Webber C, Devine SE. Natural genetic variation caused by small insertions and deletions in the human genome. Genome Res. 2011 Jun;21(6):830-9. PMC3106316